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Metabolic Inhibitors and Nucleotide Turnover

I. Inhibition of Uptake of Radiophosphate in Rat Liver and Hepatoma Slices^*

William C. Werkheiser, Richard J. Winzler and Donald W. Visser

( Department of Biochemistry and Nutrition, University of Southern California, Los Angeles, California)

The purine analog, 2,6-diaminopurine, and the pyrimidine nucleoside analog, 5-aminouridine, have been shown to reduce the incorporation of radioactive phosphate into the phospholipids and the ribonucleic acid nucleotides of slices of rat liver and a rat hepatoma. 5-Aminouridine appeared somewhat more effective in liver than in hepatoma, while 2,6-diaminopurine was more effective in hepatoma. Inhibition by aminouridine was nearly uniform in all fractions in both tissues, while that by diaminopurine was greater in the purine nucleotides in liver and in adenylic acid in hepatoma.

Differences between the metabolism of liver and hepatoma slices have been observed. Furthermore, purine and pyrimidine analogs have each been shown to inhibit incorporation into both purine and pyrimidine nucleotides, as well as that into phospholipids.

^* This work was supported in part by a grant from the California Section of the American Cancer Society and from the National Institutes of Health. Some of the facilities were made available by the Allan Hancock Foundation.

Present address: Department of Biochemistry, Oxford University, Oxford, England.

Present address: Department of Biological Chemistry, University of Illinois College of Medicine, Chicago, Illinois.

Received 11/29/54.